Food for testing life style-related diseases

ABSTRACT

It is intended to provide a food for testing life style-related diseases which is in the form of a food easy to ingest, differing from the existing medicines such as Trelan G, and makes it possible to simultaneously and easily perform a glucose tolerance test and examine oral glucose tolerance, heperlipemia after meal and so on. Namely, a test food for testing metabolic factors causing life style-related diseases which contains 100 parts by weight of carbohydrate and from 20 to 40 parts by weight of fat. It contains from 73 to 77 g of carbohydrate and from 15 to 30 g of fat, in terms of a single test dose, and provides from 460 to 600 kcal. This test food is usable in testing many items for diabetes, obesity, circulatory diseases, hyperlipemia, hyperuricemia, hyperinsulinemia and hypertension.

TECHNICAL FIELD

The present invention relates to a food for testing a life style-relateddisease, and more particularly, to a food for testing which can besafely ingested orally and which can diagnose diabetes and glucoseintolerance, and which can simultaneously and easily detect metabolicrisk factors such as hyperinsulinemia, insulin resistance, hyperlipemia,etc.

BACKGROUND ART

In recent years, life style-related diseases have rapidly increasedalong with changes in life style such as eating habits and exercise. Forexample, diabetic patients including glucose intolerance (so-calledprediabets) continue to increase, and when left as is, severecomplications, such as angina pectoris, myocardial infarction, braininfarction, diabetic gangrene, diabetic neuropathy and retinopathy,renal failure, etc., occur. Since patients are unaware of theirsubjective symptom regarding their life style-related diseases becauseof gradual advancement, early detection of diseases is important.

Conventionally, testing for diabetes has been carried out by a glucosetolerance test. This test is a testing method in which a test solutioncontaining 75 grams of glucose (which is designated as “Trelan G (tradename),” meaning Tolerance Glucose) is administered and blood sugar andinsulin are measured by a time course. The course of treatment isdecided on the basis of glucose tolerance which is judged from a patternof change in blood sugar and insulin in blood obtained before a dose ofTrelan G and 30 minutes, 60 minutes, 90 minutes, and 120 minutes after adose of Trelan G.

Although Trelan G is a test solution approved by the Ministry of Health,Labor and Welfare of Japan as a medicament and used as a standard forglucose tolerance testing, too many factors, such as (1) the testsolution is a decomposition product of starch and not a natural food,(2) sometimes side effects, such as vomiting, diarrhea, sensation ofabdominal distension, or disagreeable sensations are produced afteringestion, and (3) blood must be collected many times, are forced onexaminees. In addition, data obtainable with Trelan G is limited toblood sugar and insulin, and only diabetes and glucose intolerance [IGT(impaired glucose tolerance), prediabets] can be diagnosed.

DISCLOSURE OF THE INVENTION

Glucose intolerance including diabetes, hyperlipemia, obesity,hypertension and insulin resistance as the common foundation have beenattracting attention as main metabolic factors in life style-relateddiseases, and they are important also from the aspect of pathologicanalysis. However, the glucose tolerance test using Trelan G hasproblems as described above. Therefore, the purpose of the invention isto provide a food for testing for simultaneously and easily detectingthe above risk factors.

In order to attain the above purpose, the present inventors havecompleted a food for testing for early and simultaneous detection ofmulti-item metabolic factors in life style-related diseases as targetedby the invention, by advancing development of a food for testing whichis in the form of a food easy to chew, differing from a medicament,which makes it possible to perform a glucose tolerance test, examineoral glucose tolerance, etc. Namely, the invention provides a food fortesting for metabolic factors in life style-related diseases asdescribed below.

(1) A food for testing for detecting metabolic factors in lifestyle-related diseases containing 100 parts by weight of carbohydratesand from 20 to 40 parts by weight of fat.

(2) The food for testing for detecting metabolic factors in lifestyle-related diseases according to the above described (1) containingfrom 73 to 77 grams of carbohydrates and from 15 to 30 grams of fat interms of a single test ingestion.

(3) The food for testing for detecting metabolic factors in lifestyle-related diseases according to the above described (2), which is inthe form of a cookie and which provides from 460 to 600 kilocalories ofingestion calories in terms of a single test.

(4) The food for testing for detecting metabolic factors in lifestyle-related diseases according to any one of the above described (1)to (3), in which a life style-related disease is one, two or morediseases selected from a group consisting of diabetes, obesity,circulatory disease, hyperlipemia, hyperuricemia, hyperinsulinemia, andhypertension.

(5) The food for testing for detecting metabolic factors in lifestyle-related diseases according to any one of the above described (1)to (4), in which the metabolic factor(s) in a life style-related diseaseis one, two or more factors selected from a group consisting of glucose,insulin, apolipoprotein B, high density lipoprotein, low densitylipoprotein, neutral fat and remnant-like lipoprotein, and insulinresistance.

(6) A diagnostic method for life style-related diseases which comprisessubjecting an examinee to ingestion of food for testing for detectingmetabolic factors in life style-related diseases containing 100 parts byweight of carbohydrates and from 20 to 40 parts by weight of fat,collecting blood from the examinee over a time course and testing formetabolic factors in life style-related diseases, and comparing resultswith a result obtained before ingestion, thereby learning of any changein metabolic factors in life style-related diseases and judging thepresence or absence of an abnormal value.

(7) The diagnostic method for life style-related diseases according tothe above described (6), in which a food for testing for detectingmetabolic factors in life style-related diseases containing from 73 to77 grams of carbohydrates and from 15 to 30 grams of fat in terms of asingle test ingestion is administered.

(8) The diagnostic method for life style-related diseases according tothe above described (7), in which a food for testing for detectingmetabolic factors in life style-related diseases which is in the form ofa cookie and which provides from 460 to 600 kilocalories of ingestioncalories in terms of a single test is administered.

The food for testing for metabolic factors in life style-relateddiseases of the invention allows simultaneous and easy detection of mainmetabolic factors in life style-related diseases in place of Trelan G.In addition, since it is in the form of a food, it can be ingested fortesting without a feeling of resistance.

BEST MODE FOR CARRYING OUT THE INVENTION

The food for testing for metabolic factors in life style-relateddiseases of the invention (hereinafter, sometimes referred simply to as“food for testing”) is in the form of a food and contains 100 parts byweight of carbohydrates and from 20 to 40 parts by weight of fat. Theform of operations and processing such as baking or boiling of ediblematerials containing carbohydrates such as starch (and additionallycontaining partly maltose, etc.) and materials containing fat. The ratioof carbohydrates and fat should finally be the above-described ratio inthe food for testing. The starch becomes digestible by changing intoalpha-starch during the cooking operations and processing.

The edible materials containing carbohydrates such as starch andmaterials containing fat may be selected according to the purposedepending on the desired form of the food. For example, when theprocessing is directed at a cookie form, the main edible materialcontaining carbohydrates (starch) is flour and the main materialcontaining fat is butter. The edible form is not particularly limitedand the cookie is preferred because of simple cooking operations andprocessing as well as ease in forming a predetermined shape and testing.For processing into a food, use of food materials other than materialscontaining carbohydrates and fat is permissible according to the desiredfood when needed for processing, and for example, a protein may becontained. In addition, partial content of natural metabolite such asmaltose or glucose is permissible in the carbohydrates.

The food for testing of the invention contains carbohydrates and fat inthe above-described ratio. When testing, an examinee receives the foodso that from 73 to 77 grams (usually, the mean standard is 75 grams) ofcarbohydrates and from 15 to 30 grams of fat are ingested in terms of asingle test ingestion. By adjusting the ingestion calories in terms of asingle test to a value from 460 to 600 kilocalories, namely to ingestioncalories of a normal breakfast, the examinee can ingest the food fortesting as though he/she had eaten breakfast.

The method for testing metabolic factors in life style-related diseaseswith the food for testing of the invention may be carried out similar tothe process with Trelan G. Namely, the presence or absence of anabnormal value is judged by checking for a change in a factor aftercollecting blood from the examinee before and after the ingestion offood for testing by a time course.

The life style-related diseases as possible targets in the invention areone, two or more diseases selected from the group consisting ofdiabetes, obesity, cardiovascular disease, hyperlipemia, hyperuricemia,hyperinsulinemia and hypertension. Use of the food for testing of theinvention enables simultaneous and multi-item testing of metabolicfactors relating to these diseases.

The metabolic factors for the above life style-related diseases includeone, two or more factors selected from the group consisting of glucose,insulin, apolipoprotein B, high density lipoprotein, low densitylipoprotein, triglyceride and remnant-like particles. Presence orabsence is judged by comparing the test values with, for example, valuesin Table 1. For insulin, IRI (immunoreactive insulin, blood insulin), aswell as AUCI (area under the curve of insulin) and AUCI×AUCG (product ofarea under the curve of insulin and area under the curve of glucose) asan indicator for insulin resistance are used as described in Table 1 asmentioned later. In Table 1, Apo-B denotes apolipoprotein B, HDL-C highdensity lipoprotein, LDL-C low density lipoprotein, HOMA HomeostasisModel assessment, TG neutral fat, and RLP-C remnant-like lipoprotein,respectively.

In the invention, indicators for various test results of metabolicfactors in life style-related diseases are exemplified in Table 1. TABLE1 Table for Judgment by Cookie Test (1) Judgment by collecting bloodReference value for judgment Blood Chemistry Fasting After 1 hour After2 hours Judgment Blood sugar (mg/dl) 110 or more and less 160 or more140 or more and less than 200 Fasting hyperglycemia, glucose than 126intolerance IGT, prediabets 126 or more 200 or more Diabetes Insulin(μU/ml) 10 or more 80 or more 40 or more Hyperinsulinemia, prediabets 50or more 35 or more (change between (change between fasting value fastingvalue and and value after 2 hours) value after 1 hour) TG (mg/dl) 150 ormore 150 or more 150 or more Hypertriglyceridemia, PPTG*¹ 40 or more 40or more (change between (change between fasting value fasting value andand value after 2 hours) value after 1 hour) RLP-C (mg/dl) 7.5 or more7.5 or more 7.5 or more Hyperremnant-like particles, PPRLP*² 2 or more 2or more (change between (change between fasting value fasting value andand value after 2 hours) value after 1 hour) HDL-C (mg/dl) 40 or less 40or less 40 or less Hyper high density lipoproteinemia LDL-C (mg/dl) 120or more 120 or more 120 or more Hyper low density lipoproteinemia Apo-B(mg/dl) 110 or more 110 or more 110 or more Hyper apolipoprotein-B-emia(2) Judgment by calculating indexes Reference value for Index itemjudgment Judgment Remarks (Calculation formula) Area under the curve ofinsulin 100 or more Insulin resistance (Fasting insulin level + 1-hourinsulin level + 1-hour (μU/ml · hr)*³ insulin level + 2-hour insulinlevel) + 2 Area under the curve of insulin × 28000 or more Insulinresistance (Area under the curve of insulin) × [(fasting glucose level +1- area under the curve of glucose hour glucose level + 1-hour glucoselevel 2-hour glucose (mg/dl · μU/ml · hr)*³ level) + 2] HOMA (mg/dl ·μU/ml) 2 or more Insulin resistance Fasting glucose level × fastinginsulin level + 405*¹PPTG (postprandial hyper triglyceridemia)*²PPRLP (postprandial hyper remnant-like particles)*³Calculation formula was defined in Endocrine Journal, 2000, 47, (5),535-542.

EXAMPLES

The following Example and Test Examples will describe the invention morespecifically.

Example 1

According to the usual production method for cookies, crude materialscontaining 100g of weak flour, 30g of maltose, 45g of butter, 10 g ofwhole egg, 5g of water, 0.5g of sodium bicarbonate and 0.6g of ammoniumcarbonate per single ingestion were mixed, and baked at 180° C. for 25minutes to produce a cookie-like food.

This food was produced with weak flour as a starch source, butter as afat ingredient, and a small amount of maltose for forming the desiredshape, with the addition of egg. The cookie contains 74.3 g ofcarbohydrates, 25.2 g of lipids and 7.0 g of protein per singleingestion, and has a caloric energy of 551 kcal. The food is suitablefor judgment of blood sugar, hyperlipemia particularly a high levelafter a meal, excess or low level of insulin secretion, ability formetabolic treatment of living organisms for sugar or fat after a meal,and efficacy of insulin concerning life style-related diseases.

Test Example 1

A cookie containing 75g of wheat starch (containing 15% of maltose), 24gof fat and 7g of protein, and having a caloric energy of 560kcal, wasadministered to a healthy group, a corpulent group, a group having anexercise regimen (at least 1 hour a day and 3 days or more a week), agroup having a life style-related disease (containing subject withsuspected life style-related disease). Blood sugar, IRI, TG, TC (totalcholesterol), RLP-C, and Apo-B were measured by PAGE (polyacrylamide gelelectrophoresis), lipoprotein analysis and leptin was measured. Breathanalysis was carried out additionally. Hereinafter, this test isreferred to as cookie test.

As a result, responses of hyper-insulinemia, hyper-triglyceridemia, andhyper-reminant-like-lipoproteinemia (postprandial dyslipidemia) wereobserved in juvenile obesity, indicating insulin resistance. Forpostprandial dyslipidemia, an increase in VLDL (very low densitylipoprotein) was mainly present and a small dense formation of remnantand LDL was partly observed. A decrease in glucose oxidation and anincrease in fatty acid oxidation were also observed. In the group havingan exercise regimen, energy consumption at rest was low in significance,which is caused by a decrease in fatty acid oxidation. On the otherhand, VO₂max (maximum oxygen uptake) clearly indicated a high value.Blood sugar and IRI responses in the cookie test showed low values, andthe area under the curve of insulin, and product of area under the curveof insulin and area under the curve of glucose, as indicators showinginsulin resistance advocated by Harano, et al. were low, indicating aremarkably high insulin sensitivity. Also, TG and RLP-C were lower incomparison with pre-ingestion values, and no postprandial dyslipidemiawas observed.

Reference values for blood glucose and insulin responses, TG, RLP-C,LDL-C, HDL-C, Apo-B and diagnosis of hyperlipemia as well as anindicator for insulin resistance are shown in Table 1. Among cases wherevalues of .LDL-C and Apo-B exceeded the fasting reference after load,the case was judged an anomaly when HDL-C decreased. In electrophoresiswith Lipophor, an increase in remnant and VLDL as well as small denseformation of LDL were also observed.

When the cookie test was performed in 40 cases with IGT, lifestyle-related diseases and suspected cases, 5% in diabetes, 30% inglucose intolerance, 50% in postprandial hyperinsulinemia, 18% inpostprandial dyslipidemia, 33 to 43% in frequency of insulin resistancewere observed as abnormalities other than abnormalities found in typicaltesting and no case was judged as normal.

From the results of the cookie test, the following findings wereobtained:

(a) A physiological test reflecting daily life as compared with theconventional method can be performed.

(b) Although a feeling of fullness is frequent, gastrointestinalcomplaints are uncommon.

(c) A reference value for hyper-insulinemia can be established and theability of secretion and activity of insulin in the presence of not onlysugar but also a fatty acid can be evaluated.

(d) Standards for postprandial dyslipidemia have been established (TG,RLP-C, small dense LDL, and remnant).

(e) The activity of insulin on lipid metabolism is made more sensitiveas compared with that on sugar metabolism. A simple insulin sensitivitytest can be formed by evaluating both.

(f) The test is useful for detection of multi-item metabolic factors inlife style-related diseases and indicators for countermeasures.

(g) When the test is used together with breath analysis, it is foundthat energy consumption at rest is low and effective, and particularly,the fatty acid oxidation is decreased in a group having an exerciseregimen.

(h) In the group having the insulin resistance such as obesity, it isfound that glucose oxidation is decreased and fatty acid oxidation issuppressed and decreased after load.

(i) In addition, for measurement of blood leptin, the value is low inthe group having an exercise regimen, and it is suggested that thedecrease participates in a decrease in energy consumption and promotionof appetite.

As a conclusion, the following can be mentioned:

(1) The testing method utilizing the cookie of the invention allowsjudgment of diabetes and glucose intolerance with the same diagnosticstandard as that utilizing Trelan G (except pancreatic exocrinesecretion disorder), and is useful as oral glucose tolerance test.

(2) Establishment of reference values for hyper-insulinemia duringfasting, after 1 hour and after 2hours is possible.

(3) Establishment of indicator for insulin resistance is possible (AUCI,AUCI×AUCG).

(4) Establishment of indicator for postprandial dyslipidemia is possible(increase of TG, RLP-C).

At the same time, the method enables detection and evaluation ofmulti-item risk factors, and is useful in early detection and asindicators for countermeasures against metabolic factors in lifestyle-related diseases regarding diabetes reserve, obesity, circulatorydisease, hyperlipemia, hyperuricemia, etc.

Test Example 2

In order to elucidate the metabolic properties and mechanism in a longterm exercise regimen by the cookie for testing of the invention andbreath analysis, the following test was carried out.

Materials and method: Male students having or not having an exerciseregimen (at least 1 hour and 3 days or more a week) were charged withrunning, and AT (anaerobic threshold) and VO₂max were measured. Energyconsumption at rest was also measured. The test cookie of the invention(containing 75 g of carbohydrates mainly consisting of wheat starch and24 g of fat) was administered, and blood examination for glucoseintolerance, postprandial dyslipidemia, hyper-insulinemia and insulinresistance as well as breath analysis were carried out.

Results: Energy consumption at rest in subjects having an exerciseregimen (exercise group) was 800 to 1,100 kcal/day/m², which was lowerby 20 to 40% than that in subjects having no exercise regimen (thenon-exercise group). This was caused by a decrease in fatty acidoxidation. However, after ingesting the cookie, exogenous fat was welloxidized. AT was observed at 8.4 Mets in the exercise group and 6.5 Metsin the non-exercise group. Oxygen uptake at VO₂max was 3,389 and 2,462ml/min, respectively. Blood sugar responses during fasting and afteringestion of the cookie and also insulin responses were significantlylower in the exercise group, indicating that insulin sensitivity wasimproved. Area under the curve of insulin, and product of area under thecurve of insulin and area under the curve of glucose, as a measure ofinsulin resistance, were significantly lower, indicating that insulinsensitivity was further strengthened. TG during fasting was low in theexercise group. According to PAGE analysis, postprandial dyslipidemia,observed in the non-exercise group, was not observed in the exercisegroup. Serum level of leptin was significantly lower in the exercisegroup. It is considered that this is an explanation of low energyconsumption and promotion of appetite.

Conclusion: The exercise group clearly showed a decrease in energyconsumption at rest, which may contribute to lower fatty acid oxidation.Oxygen uptake in AT and VO₂max was increased more than the value of thenon-exercise group, indicating that they had further effective energyuse and higher physical ability. After ingestion of the cookie of theinvention, exogenous fat was easily oxidized and an increase inmitochondrial activity was shown. Simultaneous decrease in insulinresponse and decrease in blood sugar responses indicate enhancement ofinsulin sensitivity. For TG during fasting and its increase afteringestion of the cookie, the increase in VLDL in the exercise group wasimproved via activated LPL, by improvement of the insulin sensitivityconcerning lipid metabolism. The cookie for testing of the inventionallows judgment of glucose intolerance with the same criterion as thatfor liquid glucose. In addition, postprandial dyslipidemia,hyperinsulinemia and insulin resistance can be evaluated. Furthermore,the invention can be widely used not only in testing of suspecteddiabetes but also in testing of obesity, hypertension, hyperlipemia andinsulin resistance, cardiovascular diseases as well as general testingof metabolic risk factors in life style-related diseases.

INDUSTRIAL APPLICABILITY

The food for testing for metabolic factors in life style-relateddiseases of the invention is useful for detection of multi-itemmetabolic factors and as an indicator for judgment of the effect ofcountermeasures.

1. A food for testing for detecting metabolic factors in lifestyle-related diseases comprising 100 parts by weight of carbohydratesand from 20 to 40 parts by weight of fat.
 2. The food for testing fordetecting metabolic factors in life style-related diseases according toclaim 1 comprising from 73 to 77 grams of carbohydrates and from 15 to30 grams of fat in terms of single test ingestion.
 3. The food fortesting for detecting metabolic factors in life style-related diseasesaccording to claim 2, wherein the food for testing for detectingmetabolic factors in life style-related diseases is in the form of acookie and provides from 460 to 600 kilocalories of ingestion caloriesin terms of a single test.
 4. The food for testing for detectingmetabolic factors in life style-related diseases according claim 1,wherein the life style-related disease is one, two or more diseasesselected from the group consisting of diabetes, obesity, circulatorydisease, hyperlipemia, hyperuricemia, hyperinsulinemia, andhypertension.
 5. The food for testing for detecting metabolic factors inlife style-related diseases according to claim 1, wherein the metabolicfactors in a life style-related disease is one, two or more factorsselected from a group consisting of glucose, insulin, apolipoprotein B,high density lipoprotein, low density lipoprotein, triglyceride andremnant-like particles, and insulin resistance.
 6. A diagnostic methodfor life style-related diseases, which comprises subjecting an examineeto ingestion of a food for testing for detecting metabolic factors inlife style-related diseases containing 100 parts by weight ofcarbohydrates and from 20 to 40 parts by weight of fat, collecting bloodfrom the examinee by a time course and testing for metabolic factors inlife style-related diseases, and comparing results with a resultobtained before ingestion, thereby learning of any change in themetabolic factors in life style-related diseases and judging thepresence or absence of the abnormal value.
 7. The diagnostic method forlife style-related diseases according to claim 6, wherein a food fortesting for detecting metabolic factors in life style-related diseasescontaining from 73 to 77 grams of carbohydrates and from 15 to 30 gramsof fat in terms of a single test ingestion is ingested.
 8. Thediagnostic method for life style-related diseases according to claim 7,wherein a food for testing for detecting metabolic factors in lifestyle-related diseases is in the form of a cookie and provides from 460to 600 kilocalories of ingestion calories in terms of a single test isingested.
 9. The food for testing for detecting metabolic factors inlife style-related diseases according to claim 2, wherein the lifestyle-related disease is one, two or more diseases selected from thegroup consisting of diabetes, obesity, circulatory disease,hyperlipemia, hyperuricemia, hyperinsulinemia, and hypertension.
 10. Thefood for testing for detecting metabolic factors in life style-relateddiseases according to claim 3, wherein the life style-related disease isone, two or more diseases selected from the group consisting ofdiabetes, obesity, circulatory disease, hyperlipemia, hyperuricemia,hyperinsulinemia, and hypertension.
 11. The food for testing fordetecting metabolic factors in life style-related diseases according toclaim 2, wherein the metabolic factors in a life style-related diseaseis one, two or more factors selected from a group consisting of glucose,insulin, apolipoprotein B, high density lipoprotein, low densitylipoprotein, triglyceride and remnant-like particles, and insulinresistance.
 12. The food for testing for detecting metabolic factors inlife style-related diseases according to claim 3, wherein the metabolicfactors in a life style-related disease is one, two or more factorsselected from a group consisting of glucose, insulin, apolipoprotein B,high density lipoprotein, low density lipoprotein, triglyceride andremnant-like particles, and insulin resistance.
 13. The food for testingfor detecting metabolic factors in life style-related diseases accordingto claim 4, wherein the metabolic factors in a life style-relateddisease is one, two or more factors selected from a group consisting ofglucose, insulin, apolipoprotein B, high density lipoprotein, lowdensity lipoprotein, triglyceride and remnant-like particles, andinsulin resistance.
 14. The food for testing for detecting metabolicfactors in life style-related diseases according to claim 9, wherein themetabolic factors in a life style-related disease is one, two or morefactors selected from a group consisting of glucose, insulin,apolipoprotein B, high density lipoprotein, low density lipoprotein,triglyceride and remnant-like particles, and insulin resistance.
 15. Thefood for testing for detecting metabolic factors in life style-relateddiseases according to claim 10, wherein the metabolic factors in a lifestyle-related disease is one, two or more factors selected from a groupconsisting of glucose, insulin, apolipoprotein B, high densitylipoprotein, low density lipoprotein, triglyceride and remnant-likeparticles, and insulin resistance.